It is proposed to develop theoretical models relating the rheology of blood in microvessel to the mechanical properties of individual red blood cells. The flow properties of blood are crucial both to the role of the circulation in mass transport to and from tissues, and to the mechanical load on the heart resulting from peripheral resistance. The mechanics of red cell deformation and aggregation are well understood from experimental studies. Theoretical models provide a means to predict and understand the rheological behavior of blood in microvessels, based on the mechanics of individual red blood cells. Several microvascular flow regimes will be investigated, each corresponding to a particular range of vessel diameters, as follows. (1) Motion of single red cells through openings near the minimum size which permits passage of intact cells (diameter range 2-4 mum). (2) Motion of red blood cell in uniform microvessels under conditions of "multi-file" flow, in which each vessel cross- section may contain two or more red cells (6-12 mum). (3) Blood flow in microvessels at low flow rates such that effects of aggregation and sedimentation are significant (30-300 mum). These flow regimes have been chosen for their relevance to microcirculatory physiology, and represent natural continuations of work already carried out in this project. The proposed studies are expected to yield insights into the microvascular rheological behavior of blood in both normal and abnormal states. The physiological significance of model predictions will be carefully examined. Also, the models will provide a basis for assessing changes in blood rheology under conditions such as occur in low-flow states, in tumors subject to hyperglycemia, and in disorders such as diabetes. Particular emphasis will be given to comparisons between model predictions and corresponding experimental observations, taking advantage of well- established consultative and collaborative arrangements with experimental hemorheologists.